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Aortic regurgitation (AR)

The regurgitation of blood from the aorta to the left ventricle through the aortic valve in diastole.Causes of aortic regurgitation (AR)AR can be caused by primary disease of the aortic valve leaflets and/or abnormalities of the aortic root geometry. The two most common causes of AR is an abnormality (dilation) of the aortic root and degenerative calcification of the aortic valve. Another common cause is bicuspid aortic valve, which is a congenital abnormality, in which the valve has two cusps (instead of the normal three cusps, named right coronary cusp, left coronary cusp and noncoronary cusp). Bicuspid aortic valve causes more often valvular stenosis than regurgitation, but regurgitation is not infrequent in this condition. Other causes of AR are infective endocarditis (it is a cause of acute AR), rheumatic fever, in case of a prosthetic valve: degeneration, paravalvular leak or malfunction. Some more causes (that are due to damage of the leaflets) : trauma, myxomatous degeneration of the aortic valve leaflets, congenital conditions such as a subaortic membranous stenosis or a subaortic ventricular septal defect, drugs (ergot derivatives, fenfluramine).Causes of AR due to aortic root disease are:Degenerative dilatation of the aorta age-or hypertension-related.Dilatation of the aorta due to cystic medial necrosis. This condition, when it is an isolated finding is called annuloaortic ectasia. When it is not an isolated finding, then it is associated with a syndrome, such as Marfan's, or Ehlers Danlos, or osteogenesis imperfecta.Aortic dissection involving the ascending aorta can cause acute AR.Arteritis of the aorta caused by giant cell arteritis, seronegative arthropathies (ancylosing spondylitis, psoriatic arhritis, Reiter syndrome, reactive arthritis), Adamantiadis-Behcet syndrome.Pathophysiology and haemodynamic consequences of ARIn AR there is left ventricular (LV) volume overload because a larger volume of blood enters the left ventricle (LV) in diastole: Besides blood retuning from the pulmonary veins, there is also a volume of blood that regurgitates from the aorta into the LV (regurgitant volume) in diastole. The LV works with an increased in total stroke volume, which is the sum of effective stroke volume plus regurgitant volume.Aortic regurgitation also causes an increased pulse pressure, with low arterial diastolic pressure (because of the regurgitation of blood from the aorta in diastole) and increased systolic blood pressure (because of the larger stroke volume ejected by the LV in systole). The pulse pressure is the difference: systolic minus diastolic pressure. LV end-diastolic pressure and LV end-diastolic volume are increased in aortic regurgitation (AR) because, as mentioned above, a larger volume of blood enters the left ventricle in diastole. This situation leads to eccentric myocardial hypertrophy. An increase in LV end-diastolic volume is also the main com­pensatory mechanism to maintain an adequate effective stroke volume.Left ventricular ejection fraction (EF) is initially normal, however, LV end­ diastolic pressure rises. Due to the chronic overload of the left ventricle in severe AR, as the disease progresses, EF decreases over time and this together with a further increase in LV volume, may precede the onset of symptoms. Acute aortic regurgitation (causes : infective endocarditis, dissection of the ascending aorta, and trauma), also causes volume overload of the left ventricle (LV), but in this case the hemodynamic burden imposed on the LV is sudden, and so the LV does not have the time to compensate by dilatation and hypertrophy. For this reason acute severe AR can be life-threatening. A regur­gitant volume that would be well tolerated in chronic AR can lead to marked increases in LV end-diastolic pressure and a decrease in effective stroke volume. So acute AR can often lead to pul­monary edema, hypotension, and even cardiogenic shock. Indeed, in acute severe aortic regurgitation there is usually dyspnea or pulmonary edema with a normal left ventricular size and high ejection fraction.Clinical presentation of chronic severe aortic regurgitation:Patients with chronic aortic regurgitation can be asymptomatic formany years, with symptoms developing in the late stages. The most common symptom is dyspnea (shortness of breath), initially during exercise, later also at rest. Other symptoms include palpitations due to ventricu­lar or supraventricular arrhythmias, or a sensation of a prominent heart beat (due to the increased total stroke volume). Some patients also have angina, even in absence of coronaryartery disease, because of increased myocardial oxygen demand. Physical examination in aortic regurgitationA characteristicdiasto­lic murmur, high-pitched, decrescendo (intensity shows a progressive decrease during diastole) can be heard at left sternal border, 3rd-4th intercostal space. If AR is due primarily to aortic root dilatation, then the diastolic murmur usually is best heard at the second right intercostal space.The intensity of the aortic component of the second heart sound (A2) is decreased. The intensity of the AR diastolic murmur increases when the patient is sitting and leaning forward (this is also the best patient position for the murmur to be auscultated) or when the patient is squatting. The murmur intensity decreases with the strain phase of the Valsalva maneuver. The severity of aortic regurgitation correlates with duration, not intensity, of the murmur. In moderate to severe AR, a short mid-systolic flow murmur can be present at the second right intercostal space (due mostly to volume overload, causing increased flow through the aortic valve in systole, but concomitant aortic stenosis can also be present). In severe AR third heart sound (S3) is often heard, as a manifestation of the volume overload and it does not necessarily indicate congestive heart failure. Some patients with aortic regurgitation also have an Austin -Flint murmur (diastolic rumble at the apex).Pulse pressure is widened, with low diastolic and increased systolic blood pressure. In severe AR the pulse pressure is usually 100 mmHg or higher and the diastolic pressure 60 mmHg, or less.A useful clinical sign that can exclude hemodynamically significant AR is a normal or elevated diastolic blood pressure. Corrigan's pulse is observed in aortic regurgitation due to the wide pulse pressure. It is characterized by a rapid carotid upstroke followed by sudden collapse.The left ventricular apical impulse is hyperdynamic (prominent),broadened and is displaced laterally and inferiorly.Peripheral signs, related to wide pulse pressure can be present:Traube sign: pistol-shot murmur heard over the femoral arteryDuroziez sign: a murmur over the femoral artery when it is partiallycompressed.Quincke pulse: visible capillary pulsation in the nail bed after holding the tip of the nail.Musset sign: head bobbing with each cardiac cycleMüller sign: pulsation of the uvula.The ECG in chronic severe aortic regurgitation usually shows evidence of left ventricular enlargement (eccentric hypertrophy) which electrocardiographically has almost the same pattern with left ventricular concentric hypertrophy, with increased amplitude of the R waves in leads V5, V6, and of the QS, or S wave in lead V1, due to the increased left ventricular electrical forces. The T waves often are upward and tall (this is a difference from the usual strain pattern seen in concentric LV hypertrophy-e.g. in aortic stenosis). However, later in the course, T waves may become inverted. The appearance of a new conduction abnormality (e.g a left bundle branch block) in a patient with severe AR, often signifies the development of LV dysfunction.

Left ventricular size : increased (always in chronic severe AR, but often is normal in acute AR)In cases where echocardiographic assessment of the severity of aortic regurgitation is inadequate, magnetic resonance imaging (MRI), or left cardiac cathetrerization with aortography, is useful for assessing the severity of AR.Treatment of aortic regurgitation (AR)In cases of rheumatic etiology, antibiotic prophylaxis for rheumatic fever is indicated.Vasodilator treatment in AR, with ACE inhibitors and dihydropyridine calcium channel blockers (e. g. nifedipine) being the preferred drugs, is indicated if :There is systemic hypertensionThere are symptoms, or left ventricular (LV) dysfunction (in these cases surgery is the definitive treatment).There are no recommendations for vasodilator treatment in asymptomatic patients with severe AR without hypertension and LV dysfunction. Beta-blockers should be better avoided in severe AR, because by slowing the heart rate they increase the duration of diastole (and this may increase regurgitation, since AR occurs in diastole) and also because of their negative inotropic action (reduction of the force of contraction).In acute severe aortic regurgitation vasodilators (intravenous nitroprusside) and also inotropes (dobutamine or dopamine) may be needed to stabilize the patient, while preparing for surgery. Surgery must be performed promptly. Important: Which invasive treatment often used to stabilize patients with low cardiac output is contraindicated in AR ?Answer:Intraortic balloon counterpulsation is contraindicated in AR ( it could increase regurgitation, since the balloon of the intraortic balloon pump dilates in diastole).Indications for surgery in chronic severe aortic regurgitation (AR)In patients with symptoms, due to the AR (regardless of LV function)In patients with impaired left ventricular (LV) function (ejection fraction EF < 50%)In patients with severe dilatation of the LV (LV end systolic dimension > 50 mm, or LV diastolic dimension > 75 mm)(Mnemonic : "the rule of 50s" regarding the indications of surgery in severe asymptomatic chronic AR: EF <50, LVend systolic dimension > 50)In patients with severe or moderately severe AR undergoing heart surgery for another reason, such as coronary artery by-pass grafting (CABG), an aneurysm of the ascending aorta, or surgery of another valve, the aortic valve should also be replaced (This way, a possible second heart surgery in the future, for the AR is avoided. A second heart surgery carries increased surgical risk compared to the first)A useful video :

What is pressure, what is force and what is afterload? (Some physics)

Pressure (P) is the force applied perpendicular to the surface of an object per unit area, therefore it is force (F) divided by surface area (A)P = F / AForce is the physical quantity, that acting on a body can cause acceleration (change in its velocity) or distortion (a change in its shape).Elevated blood pressure causes an increase in left ventricular afterload. The afterload is the force that the heart must overcome in order to eject blood.The afterload is usually expressed as ventricular wall stress and, denoted as σσ = P r / h = Pd / 2h(P is the pressure inside the ventricle, r the radius, h the wall thickness and d of the diameter of the ventricle).This equation shows, that for a given pressure, the wall tension and hence the afterload increase with increasing radius (ventricular dilatation). Also, an increase in pressure causes an increase in the afterload. Instead, increasing the thickness of the walls of a cardiac ventricle (hypertrophy) is an adaptive mechanism that reduces the afterload. (However, hypertrophy is harmful because it is associated with increased myocardial oxygen needs and with increased risk for future adverse cardiovascular events.) Hypertrophy allows more sarcomere units to share wall tension.To summarize, the left ventricular afterload increases with:An elevation of blood pressure and systemic vascular resistance,Stenosis (narrowing) of the aortic valve Left ventricular distension (increased left ventricular dimensions)A significant increase of the afterload can lead to a reduction of the systolic performance of a cardiac ventricle. Then it can cause a reduction in stroke volume and an increase in the end-systolic volume.

Definition of arterial hypertension

Arterial Hypertension is defined as systolic blood pressure (BP) ≥140 and /or diastolic ≥ 90 mmHg at least twice on two separate visits, unless stage 2 hypertension (systolic BP ≥ 160 mm Hg, or diastolic BP ≥ 100 mm Hg) is diagnosed on the first visit, or the need for medication to keep the blood pressure < 140/90. Blood pressure (BP) should be taken in a seated position, with the arm supported, the patient at rest for 5 minutes, and without recent smoking or caffeine intake.Generally, patients should be informed that a single elevated BP measurement, does not suffice for the diagnosis of hypertension and should lead to observation and repeated measurements on different occasions.

Hypertension is a modifiable risk factor for heart disease, stroke, and chronic kidney disease. In people of middle or old age an increment of the systolic BP by 20 mmHg or of the diastolic BP by 10 is associated with a 2-fold increase in mortality risk from ischemic heart disease or stroke (cerebrovascular accident).Hypertension is a risk factor, predisposing for cerebrovascular accident (CVA),systolic heart failure, diastolic heart failure, coronary artery disease (CAD)-myocardial infarction, sudden death, atrial fibrillation and peripheral vascular disease (PVD). It is associated with increased total mortality among men and women of all ages and ethnic groups, regardless of CAD. The positive correlation between blood pressure (BP) and cardiovascular mortality (i.e.the correlation between increased BP and increased propability of death from a cardiovascular cause) is stronger for systolic BP than for diastolic. Raised diastolic BP also increases cardiovascular morbidity and mortality but less than raised systolic BP). Older age is related to an increase in systolic BP, whereas diastolic BP after age 60 tends to plateau or fall. So, older age is related to an increase in pulse pressure=the difference between systolic and diastolic BP. This is caused by a reduction in the compliance (elasticity) of the large arteries. Isolated systolic hypertension (systolic BP >140 and diastolic < 90), is the predominant form of hypertension in the elderly.Hypertension is very common, estimated to be present in 25-30 % of the adult population in western countries. The prevalence (frequency) of hypertension increases with age (> the age of 55 years more than 50% of the people have hypertension).

Classification of hypertension

The World Health Organization, International Society of Hypertension, European Society of Hypertension, and the European Society of Cardiology have published a classification of hypertension.

An interesting fact is, that individuals that do not have hypertension, but have systolic BP in the range of 120-139 and/or diastolic BP 80-89 have a higher incidence of cardiovascular events than people with optimal BP (systolic <120 mm Hg and diastolic <80 mmHg).

For children and adolescents the blood pressure (BP) limits are different (lower):It is recommended to measure BP as a routine practice on examination of children ≥ 3 years of age. Hypertension in children and adolescents is defined as systolic or diastolic BP ≥ 95th percentile in repeated measurements (ie, a pressure equal to or above the value, below which the BP of 95% of children of the same age and sex is found.). Systolic and diastolic BP percentiles based on age and gender can be found in specific tables. Pre-hypertension in children and adolescents is defined as systolic or diastolic BP between the 90th and 95th percentile. In this link you can see blood pressure percentiles for boys and girls by age and height. LINKhttps://www.nhlbi.nih.gov/files/docs/guidelines/child_tbl.pdf

Pathophysiology of hypertension

The etiology and pathophysiology of essential (primary) hypertension is multifactorial. Hypertension results from a gain in function of neural, hormonal, or renal mechanisms that induce vasoconstriction and renal sodium retention or a reduction in function of mechanisms that promote vasodilation and renal sodium excretion. Factors enhancing mechanisms that promote hypertension include: Genetic predisposition (Studies using twin data and data from Framingham Heart Study families reveal that the etiology of essential hypertension includes a substantial heritable component, ranging from about 30-55%. Further studies have shown that many different genes predispose to hypertension).Behavioral factors: Excess dietary salt intake, increased consumption of calories resulting in obesity (a predisposing factor for hypertension-especially abdominal obesity), increased alcohol consumption.Increased adrenergic tone. Neurohormonal activation contributes to the early pathogenesis by adversely affecting vascular function (e.g.,reduction of endothelium-dependent vasodilation).

(Left ventricular hypertrophy is secondary to pressure overload and neurohormonal effects).2. Adrenergic stimulation of the heart,and 3. At later stages dilation (increased dimensions and volume) of the left ventricle.

Evaluation of hypertension

Evaluation of hypertensionis conducted through the medical history, physical examination, laboratory tests, and other diagnostic procedures. Evaluation has the following goals: To identify known causes of high blood pressureTo assess the presence or absence of end-organ damage and cardiovascular disease and the severity of the disease.To identify other cardiovascular risk factors or concomitant disorders that may influence prognosis and guide treatment.Hypertension is asymptomatic in most cases, although a patient will occasionally complain of headache. If left untreated, later in the course symptoms of a cardiovascular complication may appear (for example symptoms of a stroke, or heart failure, or coronary artery disease). A history of cardiac or neurologic symptomsshould be sought and the cardiovascular system should be examinedin detail.Clinical signs of an underlying cause should be sought (radiofemoral delay or weak femoral pulses in aortic coarctation, renal enlargement in polycystic kidneys, an abdominal bruit in renovascular hypertension, caused be renal artery stenosis or cushingoid features. Also, clinical signs of target-organ damage should be sought (signs of heart failure, a palpable abdominal aortic aneurysm, a carotid or femoral bruit, retinopathy).

Findings suggesting the presense of hypertensive heart disease (a form of target organ damage) are the auscultation of a fourth heart sound (S4 gallop), or features of left ventricular hypertrophy (LVH) in the ECG or echocardiogram (which is more sensitive than the ECG for LVH). ECG evidence of LVH is associated with an about 3-fold increase in cardiovascular events. LVH is more powerful than the other 'traditional" cardiovascular risk factors for predicting an adverse outcome in hypertensive patients (such as the development of heart failure, stroke, myocardial infarction or death). In terms of estimated left ventricular mass (with echocardiography) the threshold for LVH in men is > 115 g/m2 and in women > 105 g/m2..LVH is associated with increased risk of developing myocardial ischemia (due to increased myocardial oxygen demand and increased resistance of the coronary arterial system), increased frequency of ventricular arrhythmias and diastolic dysfunction. Diastolic dysfunction, if severe, can lead to dyspnea on exertion and even pulmonary edema, in patients with normal left ventricular ejection fraction.Findings of target organ damage (for example LVH) in a patient with stage-1 hypertension indicate the need for earlier and more aggresive antihypertensive treatment.Grading of hypertensive retinopathyGrades I-IV I. Tortuous arteries, with thickened bright walls ("silver wiring") II. Narrowing in a vein where crossed by an artery III. Small retinal bleeds ("flame haemorrhages") and exudates (described as "cotton wool spots").IV. Papilloedema ( Optic disc swelling that is caused by increased intracranial pressure, or malignant hypertension..The optic disc represents the beginning of the optic nerve because it is the point where the axons of retinal ganglion cells come together. The optic disc is also the entry point for the retinal blood vessels).Ultrasound examination of the carotid arteries with measurement of the intima-media thickness (IMT) and detection of atheromatous plaques has also prognostic significance. An increased IMT ≥ 9 mm, or the presense of plaques are findings that indicate target organ damage (of the arterial system) and increase the risk of a stroke or a myocardial infarction. Treatment of hypertension

The objective of antihypertensive therapy is to reduce the incidence of adverse cardiovascular events (i.e. to reduce the long term risk of cardiovascular mobidity and mortality). The benefit of therapy of hypertension is a reduction in the risk of stroke by about 30% and in the risk of coronary atery disease (CAD) by 20%.Placebo-controlled trials have proven that any blood pressure lowering drug treatment reduces strokes, the incidence of heart failure, coronary events, and deaths in hypertensive patients and this is true even for elderly patients > 80 years.According to current guidelines, the goal of treatment for all hypertensive patients, even in high risk patients with diabetes or chronic kidney disease, or indications of target organ damage is systolic pressure < 140 and diastolic < 90 mmHg. An exception are very elderly patients 80 years or older where the goal is to slowly achieve systolic BP < 150.Lifestyle modification should be the first line of treatment for patients with hypertension. Start with lifestyle modification even if drug therapy is also needed. Lifestyle measures include the following: Restricting salt (a low sodium intake of 100 mmol/day, i.e. 6 g NaCl, or less), starting a diet high in fruits, vegetables, and low-fat dairy products (Dietary Approaches to Stop Hypertension -DASH) diet plan), correcting obesity (weight loss with a goal of achieving a body mass index <25 kg/ m2of body surface area can improve hypertension control),reducing alcohol intake,smoking cessation and taking regular physical exercise. Moderately intense physical activity (e.g., brisk walking, or cycling) for 30 minutes or more, four or more times a week, is beneficial for BP lowering.There are no strong recommendations for altering caffeineintake. Chronic caffeine intake has not been shown to correlate with elevated blood pressure (BP), but propably excessive caffeine intake should be discouraged, because caffeine can lead to transient elevations in BP.Relaxation therapy and stress management can be useful in some cases, but generally they are of uncertain benefit.

When medications are needed, adequate control of hypertension is more important than the category of medication used, with the exception of compelling indications. Compelling indications are indications, in case of patients who have other coexisting health problems, to use the drug category, which is more suitable for the specific coexisting diseases (comorbidities).

According to the latest guidelines (JNC 8) four classes of antihypertensive drugs are recommended as choices for first line treatment (initial drug choices). The physician should choose one of the following for treatment initiation: These are an angiotensin-converting enzyme inhibitor (ACEI), or an angiotensin receptor blocker (ARB), a calcium-channel blocker (CCB), or a diuretic (D), usually a thiazide type diuretic (but in patients with moderate to severe renal dysfunction thiazide diuretics have reduced effect and a loop diuretic can be used instead). This selection of first line drugs is based on evidence from randomized control trials (RCTs). In the general population, including those with diabetes mellitus, treatment should start with these drugs either with one drug (monotherapy, usually selected in cases of stage 1 hypertension), or with a combination of 2 drugs from these categories (usually selected for stage 2 hypertension, i.e systolic BP ≥ 160 and/or diastolic BP ≥ 100).In most cases, choose agents with 24-hour duration of action and once-daily dosing, for better patient compliance.When a drug combination is needed, any of these drug categories can be combined with each other, in combinations of 2 (or if necessary 3) drugs, with one exception : A combination of ACEIs and ARBs is not preferable and should generally not be used. (This combination is used for some patients with systolic heart failure and persistent symptoms, who are intolerant to mineralocorticoid antagonists, but in this case the goal of treatment is to treat heart failure, not hypertension- see chapter on Heart Failure)In patients with chronic kidney disease (CKD), antihypertensive treatment should start with either an ACEI or an ARB, because these drugs have been shown to demontrate renoprotective effects.In the general black population, including patients with diabetes mellitus, treatment for hypertension should start either with a thiazide-type diuretic or with a calcium channel blocker (CCB), because ACEIs and ARBs, generally have been found not to achieve an adequate control of hypertension in black people. Monotherapy is successful in approximately 40% of patients, but in the rest (about 60%), to attain goal BP, a combination of two or more drugs will be needed. The latter is oftenthe rule in patients with a BP > 160/100 mm Hg.If there is a partial but inadequate response to the first antihypertensive drug, or to the initial drug combination used, either increase the dose of the first drug, or a drug included in the initial combination, or add an agent from a different class. Every dosage adjustment should be within the recommended dose limits of each drug (mentioned in textbooks, guidelines, or in the summary of product characteristics published for each drug). Dose increments generally should be gradual and moderate, not sudden and "agressive", especially in elderly patients and a renal or hepatic dysfunction, or any other comorbidity, should be taken into account, if present. The previous guideline, JNC 7, recommended five drug classes as initial therapy, which include the above 4 classes and beta-blockers, emphasizing the use of thiazide diuretics for most patients, who do not have a compelling indication for a specific class. In patients whose goal blood pressure (BP) cannot be reached with 3 agents from the first line drug classes, agents from other drug classes should be added.

Beta-blockers (BB) are not recommended as initial therapy for patients with hypertension in the recent guideline of JNC (JNC 8). They should be used as initial therapy, only if a compelling indication is present (for example angina, previous myocardial infarction, heart failure with reduced ejection fraction, tachyarrhythmias). The exclusion of beta-blockers from first- line drugs in JNC 8 was related to less satisfactory results in blood pressure (BP) lowering and a smaller reduction of the overall cardiovascular mortality in the general hypertensive population with beta blockers in comparison to the 4 other first-line drug categories.

Resistant hypertension (RH)

RH is systolic BP >140 and/or diastolic BP> 90 mmHg despite adequate doses of three or more antihypertensive medications , including a diuretic for at least 1 month, or hypertension requiring 4 or more antihypertensive drugs, in order to be adequately controlled. Resistant hypertension can be real or spurious (not real resistance to treatment). Causes of spurious resistant hypertension:

Non-adherence to treatment (common phenomenon: many patients do not take their medications according to the prescription, "forget" doses, etc).

White coat hypertension: Persistence of an alerting reaction to the BP-measuring procedure : BP is elevated at the doctor's office, but home BP measurements are normal.

Technical errors in measurement: Use of small cuffs on large arms, leading to inadequate compression of the artery.

Pseudo-hypertension: Marked arterial stiffening in elderly persons with heavily calcified arteries. This prevents occlusion of the brachial artery by cuff pressure and leads to measuring higher BP than its real value.

Hypertensive crisis is defined as a systolic blood pressure (SBP) of 190-200 mm Hg or greater and/or a diastolic blood pressure (DBP) of 120 mm Hg or greater. It is a broad term encompassing hypertensive urgency and emergency. Patients without acute or rapidly developing end-organ damage are classified as having a hypertensive urgency. When individuals meet the criteria for hypertensive crisis and also have evidence of rapidly progressive target organ dysfunction (end-organ damage), it is a hypertensive emergency. The rate of change in BP is important. A rapid rise is poorly tolerated and leads to end-organ damage, whereas a gradual blood pressure rise in a patient with preexistent poor BP control is tolerated better. A hypertensive urgency or emergency can occur in patients with primary or secondary hypertension (for example renovascular hypertension, acute glomerulonephritis, scleroderma, pheochromocytoma, thyrotoxicosis, eclampsia and pre-eclampsia, etc).

Hypertensive emergencies typically present as sudden, high elevations in blood pressure associated with acute target organ dysfunction. Presentations include hypertensive encephalopathy, malignant hypertension, acute coronary syndromes, acute pulmonary edema, acute cerebrovascular events, aortic dissection, eclampsia and acute renal dysfunction. The initial examination should include a focused history, cardiovascular, mental and funduscopic examinations, as well as pertinent laboratory values.Once the diagnosis of a hypertensive emergency has been made, drug therapy should be initiated promptly, even before laboratory results are available.

Malignant hypertension is a medical emergency, diagnosed when there is severe hypertension (systolic blood pressure > 200 mmHg ± diastolic blood pressure > 130, (typically there is BP above 220/130 mmHg) ,together with retinopathy, of grade III-IV. Headache is often present and occasionally visual disturbance (blurred vision), nausea and vomiting. Besides headache and blurred vision, more severe manifestations of central nervous system dysfunction can also be present, such as confusion and seizures (hypertensive encephalopathy) with or without manifestations of acute heart or renal dysfunction, such as pulmonary edema and oliguria. Hypertensive encephalopathy requires differential diagnosis from an intracranial hemorrhage or an acute ischemic stroke. A new focal neurologic deficit suggests an ischemic stroke in evolution. Brain CT or MRI may be needed to aid the diagnosis. An ischemic stroke demands a much more conservativeapproach to hypertension (gradual and not rapid pressure lowering) in comparison to hypertensive encephalopathy, which demands a more rapid pressure lowering to a BP, initially about 160-170/100-110. Laboratory findings in malignant hypertension: Proteinuria and hematuria are often present. In cases of malignant hypertension, immediate treatment is required to prevent complications, such as rapid progression to renal failure, heart failure, or stroke. If malignant hypertension is untreated, the 1-year mortality is approximately 90 %. In a hypertensive crisis, rapid lowering of BP may compromise tissue perfusion, leading to cerebral damage or to coronary or renal insufficiency. Thus, rapid reduction of BP must be avoided, because it can result in cerebral and cardiac hypoperfusion (abrupt change of >25% in BP will exceed cerebral BP autoregulation).A good rule is to lower initially the elevated BP by 10% in the first hour and by an additional 15% during the next 3 to 12 hours to a blood pressure of no less than 160/100-110 mmHg.This rule has some exceptions, where BP must be lowered more rapidly. Such situations are aortic dissection, postoperative hemorrhage and acute myocardial infarction. Most patients, with a hypertensive crisis, in the absence of manifestations of acute target organ damage, even if blood pressure (BP) is 220/130 mmHg or higher, should be treated with short-acting oral medications. First-line treatment should be with a diuretic, a beta-blocker (unless contraindicated) ,a low-dose calcium antagonist, or an ACE inhibitor. A combination of two or more of these drug-classes may be needed. (Sublingual nifedipine should be avoided because it can result in rapid changes in blood pressure). In real hypertensive emergensies with manifestations of acute target organ damage, the patient is admitted to an intensive care unit (ICU) and antihypertensive treatment starts with intravenous agents.Where necessary, intravenous administration of: labetalol, nitroglycerine (GTN-glycerine trinitrate) and sodium nitroprusside are effective treatment options. Intravenous treatment requires careful patient supervision. Labetalol is the drug of choice in pheochromocytoma, or aortic dissection. It must be avoided if there is left ventricular failure.Intravenously (IV) it is given as a bolus of 20–80 mg and administration is continued with IV infusion, (20–200 mg/min, start with a low dose and increase every 15 minutes, if needed for blood pressure control. IV treatment has an onset of action after 2-5 minutes. Labetalol can be continued orally (PO) 100–400 mg /12 hours. If the patient does not need parenteral treatment (in less severe emergencies) treatment can start PO. Then the onset of action is in 30-60 minutes (min). It is also safe for pregnant patients. Nitroprusside is the drug of choice for hypertensive emergencies with acute left ventricular failure and/or hypertensive encephalopathy. It is administered by IV infusion 0.25–10 µg/kg of body weight/min and the onset of action is in seconds.Nitroglycerine is useful in hypertensive emergensies with left ventricular failure or acute coronary ischemia. It is given in IV infusion 1–10 mg/hour and the onset of action is in 2-5 minutes. Hydralazine is given IV 5–10 mg over 20 minutes and then by IV infusion 50–300 µg/min (µg = microgram= 10-6 gram).Esmolol HCl is a short-acting beta-blocker (it is also used for supraventricular tachycardias) It is given in a IV loading dose500 µg/kg/min and continuous IV infusion 50–200 µg/kg/min.

Hypertensive disorders of pregnancy are the most common medicaldisorder in pregnancy. Hypertension is estimated to occur in5% - 10% of all pregnancies and it is a major cause of maternaland fetal morbidity and mortality.Hypertension in pregnancy is defined as blood pressure (BP) ≥ 140/90 in two measurements, at least 4 hours apart.Hypertension in pregnancy includes 5 categories :Chronic hypertension. It refers to hypertension that has appeared prior to pregnancy or before 20 weeks of gestationGestational hypertension:The development of hypertension without proteinuria after 20 weeks of gestation. It can evolve into preeclampsia.Preeclampsia: Hypertension in a pregnant woman accompanied by proteinuria (pathologic excretion of protein in the urine) >300mg/24 hours, developing after 20 weeks of gestation. Preeclampsia is more common in women with multiple gestations, a history of hypertension for 4 years or more, renal disease, history of hypertension in a previous pregnancy, family history of preeclampsia. Preeclampsia can progress to eclampsia (in this case seizures appear).Chronic hypertension with superimposed preeclampsia:When in a woman with hypertension, there is a new onset of proteinuria after 20 weeks of gestation. In a woman with hypertension and proteinuria prior to 20 weeks of gestation, superimposed preeclampsia is recognised by a sudden 2-3 fold increase in proteinuria, or the development of thrombocytopenia (pathologic reduction of the platelet count in the blood), or the development of an elevation of alanine aminotransferase (ALT), or aspartate aminotransferace (AST).Transient hypertensionThis is a retrospective diagnosis. It denotes hypertension in pregnancy with subsequent normalization of blood pressure in 12 weeks postpartum. It may predict reoccurence of hypertension in a next pregnancy, or the later development of primary hypertension. The pathophysiology of hypertension in pregnancy includes an increased cardiac output and vasoconstriction due to an increased central and peripheral sympathetic activity.Preeclampsia is associated with an immunologic mechanism.

Treatment of hypertension in pregnancy

Women with stage 1 hypertension (systolic BP 140 to 159 mm Hg or diastolic BP 90 to 99 mm Hg) are low risk for cardiovascular complications in pregnancy and they are treated with lifestyle modification only (salt restriction) and a restriction of physical activity. Women with target organ damage should receive antihypertensive medication. Women with prior requirement for multiple antihypertensive agents to control their BP, should also receive medication.If blood pressure (BP) reaches 160 systolic or 100 diastolic, treatment with antihypertensive medications should be instituted in every case. Effective treatment of severe hypertension especially in the first trimester of pregnancy is mandatory. Treatment for preeclampsia includes hositalization, bed rest, control of BP, seizure prophylaxis (treatment with magnesium sulphate) if signs of impending eclampsia develop and timely delivery. Magnesium sulphate has shown excellent results in the prevention and treatment of convulsions. Delivery should be strongly considered regardless of gestational age if there are signs of fetal distress, or signs of maternal problems including severe hypertension, headache, visual disturbance, epigastric pain, deteriorating renal function, elevated liver enzymes, hemolysis, low platelet count. Antihypertensive drug treatment in pregnancy.Methyldopa is generally preferred (first line drug in pregnancy ) because it does not affect uteroplacental blood flow and does not have short or long-term adverse effects on the development of children. Labetalol can also be used as a first -line drug instead of methyldopa. Beta adrenergic blockers and the calcium channel blocker nifedipine, are generally safe and can be administered for the treatment of hypertension in pregnancy, but there are some reports of fetal growth retardation with the beta-blocker, atenolol. Diuretics are considered relatively safe but they should not be used as first-line agents. Pregnancy is a contraindication for ACE-inhibitors and angiotensin receptor blockers (ARBs) and this a fact that every physician should remember.A USEFUL LINK ESC Guidelines on the management of cardiovascular diseases during pregnancy

Echocardiography in hypertension and echocardiography in diastolic dysfunction.

Hypertensive heart disease can be deﬁned as the response of the heart to the increased afterload, imposed on the left ventricle by the increased arterial pressure and total peripheral resistance, as a consequence of hypertensive vascular disease. Usual sequelae of hypetrension are the following: left ventricular hypertrophy, diastolic dysfunction, cardiac arrhythmias, congestive heart failure and ischemic heart disease. Depending on the severity of hypertensive heart disease a patient can have one or more of the above disorders.

The primary echocardiographic finding in many patents with long- standing hypertension is left ventricular hypertrophy. The threshold for defining left ventricular hypertrophy in the average adult is left ventricular wall thickness> 11 mm (measured by M- mode or 2 -dimensional echocardiography). A usual additional echocardiographic ﬁnding of hypertensive heart disease is left atrial enlargement (dilation) in response to increased left ventricular diastolic filling pressures. The upper normal limit of the anteroposterior left atrial end-systolic dimension in adults is about 4cm (40 mm).Measurement of maximum left atrial volume (at end-systole) can be performed in the apical four-chamber view by the multiple discs method. (The machine divides the cavity in parallel discs and calculates the sum of their volumes).

Assesment of left ventricular diastolic function (a summary)

Another usual finding in hypertension is diastolic dysfunction which usually is mild or moderate, but in some cases it can be severe.

Diastolic dysfunction can occur in many kinds of heart disease such as hypertensive heart disease, diabetes, hypertrophic cardiomyopathy, aortic stenosis with left ventricular hypertrophy, ischemic heart disease, restrictive cardiomyopathy, constrictive pericarditis, etc.Evaluation of left ventricular (LV) diastolic function begins with M-mode and 2D echocardiography : Assessment of LV size wall thickness and of left atrial (LA) volume and antero-posterior dimension. In patients with LV diastolic dysfunction, concentric oreccentric LV hypertrophy can be found. Increased LA volume reflects the effects of the increased LV filling pressures over time. A LA volume index > 34 ml/m2 indicates left atrial dilation, which is an indication of increased LV filling pressures (this can occur in patients with diastolic or systolic dysfunction). LA dilation can also occur in patients with mitral stenosis or regurgitation.

Doppler assesment: To assess the mitral inflow align the Doppler beam with the inflow direction and place a 1–3 mm pulse wave (PW) Doppler sample volume between the tips of the mitral leaflets. If the PW sample volume position is not at the valve tips, but towards the mitral annulus or towards the apex, this can alter significantly the mitral flow velocities.E is the peak early diastolic velocity of trasmitral flow and A is the peak late diastolic velocity at the time of atrial contraction. In adults with normal diastolic function E/A has a value between 0.8 and 2, but less than 2 (In younger people E>A and in middle aged or older people E wave normally becomes lower and A increases and can be higher than A). In adults with normal diastolic function (normal pattern) the E > A but is less than 2A (except in very young persons), or E may be a little smaller than A, but more than 0,8 A (the E wave can be lower than the A wave by less than 20 %). The deceleration time of the E wave (time from the peak of the E wave to its end at the baseline) is DT = 150–200 ms and isovolumic relaxation time (the time from the end of aortic flow to the beginning of mitral flow) is IVRT = 50–100 ms. Measure isovolumic relaxation time (IVRT) by placing the PW Doppler sample volume in- between LV inflow and outflow to simultaneously display the end of aortic flow and the onset of mitral E-wave velocity. In very young people with normal diastolic function E/A can be >2, but this is not due to an increased LA pressure sa in the restrictive pattern. This pattern in young people is normal and is due to a more active relaxation of the left ventricle (LV) in early diastole, so that early diastolic flow velocity is increased. It is easy to distinguish this from the restrictive pattern, because these are very young persons with no heart disease, no symptoms of effort dyspnea, normal left atrial size and normal tissue doppler velocities of the mitral annulus.

Pulse wave doppler of pulmonary venous flow (obtained in the apical 4 chamber view) in adults with normal diastolic function and also in those with mildly impaired diastolic function (delayed relaxation) shows S ≥D. S is the peak velocity of the systolic wave and D the peak velocity of the early diastolic wave of pulmonary venous flow.

In people with normal diastolic function and also in those with mild diastolic dysfunction (impaired relaxation)

the ratio E/Ea is <10. E is the peak velocity of the early transmitral flow and Ea (or E') is the peak early diastolic velocity of the mitral annulus measured by pulse wave tissue doppler.

In more advanced forms of diastolic dysfunction (moderate or grade- 2 diastolic dysfunction with a pseudonormal pattern of trasmitral flow-see below, or severe diastolic dysfunction with the restrictive pattern), the pulmonary venous flow shows S<D and tissue doppler of the mitral annulus shows E/Ea ≥ 10 and a reduced velocity Ea.Mild (grade 1) diastolic dysfunction is characterized by the impaired relaxation (or delayed relaxation) mitral inflow pattern with E/A< 0.8 and prolonged deceleration time DT of the mitral flow E wave (a> 200 ms). DT is the time from the peak to the end of the E wave. There is also prolongation of isovolumic relaxation time, IVRT ≥ 100 ms. The IVRT is the time from the closure of the aortic valve (end of left ventricular ejection) to the opening of the mitral valve (onset of ventricular filling). In this time interval left ventricular dimensions are constant and the mitral annulus does not move. So, the IVRT can be measured on the pulse wave tissue doppler tracing of the mitral annulus as the time from the end of the systolic S wave to the onset of the Ea (E').

Moderate (grade 2) diastolic dysfunction shows the same transmitral flow pattern (0.8 < E/A <1.5) ,as that found in persons with normal diastolic function. It is called pseudonormal pattern.In the pseudonormal pattern (as well as in the normal pattern) IVRT is <100 msec and a 150 <DT <220 ms. This pattern can be distinguished from the normal pattern of diastolic inflow, because at the peak of the Valsalva maneuver (which causes a reduction of preload = a reduction of ventricular filling) in people with grade-2 diastolic dysfunction, the pattern of mitral inflow takes the morphology of impaired relaxation (E< A). Another distinguishing feature of the pseudonormal pattern is the reduced mitral annular Ea (E') velocity, the increased E/Ea ( at about 10 or more) and the pulmonary venous flow showing S<D (S/D <1).The pseudonormal mitral inflow pattern can change to a delayed relaxation pattern by reducing preload with diuretic treatment.Severe diastolic dysfunction is characterized by the restrictive left ventricular ﬁlling pattern, where the markedly elevated left atrial pressure causes an increased early transmitral pressure gradient (pressure difference between the left atrium and thw left ventricle) in early diastole. This causes the following findings: E/A ratio >2, a short deceleration time (DT <160 msec) and also short IVRT < 80 msec. Due to the severe impairment of diastolic function, mitral annular Ea (E') velocity is usually severely reduced, the ratio E/Ea is increased (>10) and pulmonary venous flow shows S<D. If the restrictive pattern is classified as stage 3 diastolic dysfunction if it can be reversed, by reducing preload with diuretic treatment, to a pattern of stage 1 or 2 diastolic dysfunction. If treatment can not change the restrictive pattern of left ventricular filling, then diastolic function is classified as stage-4 diastolic dysfunction and this carries a severe prognosis.Regarding the tissue doppler examination of the velocities of the mitral annulus, the early diastolic peak velocity of the mitral annulus (Ea) is generally a good index of diastolic function. Ea is higher at the lateral mitral annulus than at the septal annulus. An indication of diastolic dysfunction is an Ea <8.5 cm/sec at septal annulus,or <10 cm/sec at the lateral annulus. Ea has a reasonable accuracy in identifying patients with diastolic dysfunction and pseudonormal LV ﬁlling: The normal and pseudonormal filling pattern have the same pattern of transmitral flow, but in case of a pseudonormal pattern the Ea velocity is reduced. This is a feature that can distinguish it from the normal pattern. In people with cardiac disease, an increased E/Ea ratio can provide an indication about the presence of an elevated left ventricular filling pressure and pulmonary capillary wedge pressure, if the ratio is > 15 for the septal mitral annulus or > 10 for the lateral mitral annulus. In case of the septal mitral annulus, E/Ea between 10 and 15 is borderline, and cannot predict if the left ventricular diastolic pressures are elevated or normal. When an average (anterior, inferior, septal, and lateral) Ea velocity is available, a cutoff value of 15 should be considered for the E/Ea ratio.